Skip to main content
Top
Published in: BMC Oral Health 1/2021

Open Access 01-12-2021 | Research article

Expression of substance P, calcitonin gene-related peptide and vascular endothelial growth factor in human dental pulp under different clinical stimuli

Authors: Javier Caviedes-Bucheli, Luis Fernando Lopez-Moncayo, Hernan Dario Muñoz-Alvear, Jose Francisco Gomez-Sosa, Luis Eduardo Diaz-Barrera, Hernando Curtidor, Hugo Roberto Munoz

Published in: BMC Oral Health | Issue 1/2021

Login to get access

Abstract

Background

The aim of this study was to measure the dental pulp inflammatory response through neuropeptides (SP and CGRP) as a response to occlusal trauma, orthodontic movements and a combination of both, as well as the angiogenic defense mechanism through VEGF expression, which could be the initial step to mineralized tissue formation.

Methods

Forty human dental pulp samples were collected from healthy first premolars with extraction indicated due to orthodontic reasons from a sample of 20 patients. Patients were divided into four groups with 10 premolars each (1 mandibular and 1 maxillary premolar from each patient): healthy pulp control group, occlusal trauma group, moderate orthodontic forces group; and occlusal trauma plus moderate orthodontic forces group. Stimuli were applied for 24 h before tooth extraction in all experimental groups. All samples were processed, and SP, CGRP, and VEGF were measured by radioimmunoassay. The Kruskal–Wallis test was performed to assess significant differences among groups and Mann–Whitney’s U post hoc pairwise comparisons were also performed.

Results

The highest increase in SP, CGRP, and VEGF expressions was found in the occlusal trauma plus orthodontic forces group, followed by the moderate orthodontic forces, the occlusal trauma and the control groups, with statistically significant differences between all groups for each of the 3 peptides analyzed (Kruskal–Wallis p < 0.001). All possible pairwise post-hoc comparisons were also significant for each peptide analyzed (Mann–Whitney’s U p < 0.001).

Conclusion

SP, CGRP, and VEGF expressions significantly increase in human dental pulps when stimulated by occlusal trauma combined with moderate orthodontic forces, as compared with these two stimuli applied independently.
Literature
1.
go back to reference Caviedes-Bucheli J, Muñoz HR, Azuero-Holguín MM, Ulate E. Neuropeptides in dental pulp: the silent protagonists. J Endod. 2013;34:773–88.CrossRef Caviedes-Bucheli J, Muñoz HR, Azuero-Holguín MM, Ulate E. Neuropeptides in dental pulp: the silent protagonists. J Endod. 2013;34:773–88.CrossRef
2.
go back to reference Aranha AM, Zhang Z, Neiva KG, Costa CA, Hebling J, Nör JE. Hypoxia enhances the angiogenic potential of human dental pulp cells. J Endod. 2010;36:1633–7.CrossRef Aranha AM, Zhang Z, Neiva KG, Costa CA, Hebling J, Nör JE. Hypoxia enhances the angiogenic potential of human dental pulp cells. J Endod. 2010;36:1633–7.CrossRef
3.
go back to reference Lee YH, Kim GE, Cho HJ, Yu MK, Bhattarai G, Lee NH, Yi HK. Aging of in vitro pulp illustrates change of inflammation and dentinogenesis. J Endod. 2013;39:340–5.CrossRef Lee YH, Kim GE, Cho HJ, Yu MK, Bhattarai G, Lee NH, Yi HK. Aging of in vitro pulp illustrates change of inflammation and dentinogenesis. J Endod. 2013;39:340–5.CrossRef
4.
go back to reference Caviedes-Bucheli J, Gomez-Sosa JF, Azuero-Holguin MM, Ormeño-Gomez M, Pinto-Pascual V, Munoz HR. Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma. Int Endod J. 2017;50:339–51.CrossRef Caviedes-Bucheli J, Gomez-Sosa JF, Azuero-Holguin MM, Ormeño-Gomez M, Pinto-Pascual V, Munoz HR. Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma. Int Endod J. 2017;50:339–51.CrossRef
5.
go back to reference Killough SA, Lundy FT, Irwin CR. Substance P expression by human dental pulp fibroblasts: a potential role in neurogenic inflammation. J Endod. 2009;35:73–7.CrossRef Killough SA, Lundy FT, Irwin CR. Substance P expression by human dental pulp fibroblasts: a potential role in neurogenic inflammation. J Endod. 2009;35:73–7.CrossRef
6.
go back to reference Tran-Hung L, Mathieu S, About I. Role of human pulp fibroblasts in angiogenesis. J Dent Res. 2006;85:819–23.CrossRef Tran-Hung L, Mathieu S, About I. Role of human pulp fibroblasts in angiogenesis. J Dent Res. 2006;85:819–23.CrossRef
7.
go back to reference El karim IA, Linden GJ, Irwin CR, Lundy FT. Neuropeptides regulate expression of angiogenic growth factors in human dental pulp fibroblasts. J Endod. 2009;35:829–33.CrossRef El karim IA, Linden GJ, Irwin CR, Lundy FT. Neuropeptides regulate expression of angiogenic growth factors in human dental pulp fibroblasts. J Endod. 2009;35:829–33.CrossRef
8.
go back to reference Uddman R, Kato J, Lindgren P, Sundler F, Edvinsson L. Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp and trigeminal ganglion. Arch Oral Biol. 1999;44:1–6.CrossRef Uddman R, Kato J, Lindgren P, Sundler F, Edvinsson L. Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp and trigeminal ganglion. Arch Oral Biol. 1999;44:1–6.CrossRef
9.
go back to reference Tuo Y, Guo X, Zhang X, Wang Z, Zhou J, Xia L, Zhang Y, Wen J, Jin D. The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell. J Recept Signal Transduct. 2013;33:114–23.CrossRef Tuo Y, Guo X, Zhang X, Wang Z, Zhou J, Xia L, Zhang Y, Wen J, Jin D. The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell. J Recept Signal Transduct. 2013;33:114–23.CrossRef
10.
go back to reference Grando Mattuella L, Westphalen Bento L, de Figueiredo JA, Nör JE, de Araujo FB, Fossati AC. Vascular endothelial growth factor and its relationship with the dental pulp. J Endod. 2007;33:524–30.CrossRef Grando Mattuella L, Westphalen Bento L, de Figueiredo JA, Nör JE, de Araujo FB, Fossati AC. Vascular endothelial growth factor and its relationship with the dental pulp. J Endod. 2007;33:524–30.CrossRef
11.
go back to reference Saghiri MA, Asatourian A, Sorenson CM, Sheibani N. Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration. J Endod. 2015;41:797–803.CrossRef Saghiri MA, Asatourian A, Sorenson CM, Sheibani N. Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration. J Endod. 2015;41:797–803.CrossRef
12.
go back to reference Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell. 2011;146:873–87.CrossRef Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell. 2011;146:873–87.CrossRef
13.
go back to reference Wei F, Yang S, Xu H, Guo Q, Li Q, Hu L, Liu D, Wang C. Expression and function of hypoxia inducible factor-1 α and vascular endothelial growth factor in pulp tissue of teeth under orthodontic movement. Mediators Inflamm. 2015:1–9. Wei F, Yang S, Xu H, Guo Q, Li Q, Hu L, Liu D, Wang C. Expression and function of hypoxia inducible factor-1 α and vascular endothelial growth factor in pulp tissue of teeth under orthodontic movement. Mediators Inflamm. 2015:1–9.
14.
go back to reference Rombouts C, Giraud T, Jeanneau C, About I. Pulp vascularization during tooth development, regeneration, and therapy. J Dent Res. 2017;96:137–44.CrossRef Rombouts C, Giraud T, Jeanneau C, About I. Pulp vascularization during tooth development, regeneration, and therapy. J Dent Res. 2017;96:137–44.CrossRef
15.
go back to reference Ikeda T, Nakano M, Bando E, Suzuki A. The effect of light premature occlusal contact on tooth pain threshold in humans. J Oral Rehabil. 1998;25:589–95.CrossRef Ikeda T, Nakano M, Bando E, Suzuki A. The effect of light premature occlusal contact on tooth pain threshold in humans. J Oral Rehabil. 1998;25:589–95.CrossRef
16.
go back to reference Roberts-Clark DJ, Smith AJ. Angiogenic growth factors in human dentine matrix. Arch Oral Biol. 2000;45:1013–6.CrossRef Roberts-Clark DJ, Smith AJ. Angiogenic growth factors in human dentine matrix. Arch Oral Biol. 2000;45:1013–6.CrossRef
17.
go back to reference Derringer KA, Linden RWA. Angiogenic growth factors released in human dental pulp following orthodontic force. Arch Oral Biol. 2003;48:285–91.CrossRef Derringer KA, Linden RWA. Angiogenic growth factors released in human dental pulp following orthodontic force. Arch Oral Biol. 2003;48:285–91.CrossRef
18.
go back to reference Caviedes-Bucheli J, Azuero-Holguin MM, Correa-Ortiz JA, Aguilar-Mora MV, Pedroza-Flores JD, Ulate E, Lombana N, Munoz HR. Effect of experimentally induced occlusal trauma on substance P expression in human dental pulp and periodontal ligament. J Endod. 2011;37:627–30.CrossRef Caviedes-Bucheli J, Azuero-Holguin MM, Correa-Ortiz JA, Aguilar-Mora MV, Pedroza-Flores JD, Ulate E, Lombana N, Munoz HR. Effect of experimentally induced occlusal trauma on substance P expression in human dental pulp and periodontal ligament. J Endod. 2011;37:627–30.CrossRef
19.
go back to reference Caviedes-Bucheli J, Moreno JO, Ardila-Pinto J, Del Toro-Carreño HR, Saltarín-Quintero H, Sierra-Tapias CL, Macias-Gomez F, Ulate E, Lombana-Sanchez N, Munoz HR. The effect of orthodontic forces on calcitonin gene-related peptide expression in human dental pulp. J Endod. 2011;37:934–7.CrossRef Caviedes-Bucheli J, Moreno JO, Ardila-Pinto J, Del Toro-Carreño HR, Saltarín-Quintero H, Sierra-Tapias CL, Macias-Gomez F, Ulate E, Lombana-Sanchez N, Munoz HR. The effect of orthodontic forces on calcitonin gene-related peptide expression in human dental pulp. J Endod. 2011;37:934–7.CrossRef
20.
go back to reference Caviedes-Bucheli J, Lombana N, Azuero-Holguin MM, Munoz HR. Quantification of neuropeptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal polypeptide) expressed in healthy and inflamed human dental pulp. Int Endod J. 2006;39:394–400.CrossRef Caviedes-Bucheli J, Lombana N, Azuero-Holguin MM, Munoz HR. Quantification of neuropeptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal polypeptide) expressed in healthy and inflamed human dental pulp. Int Endod J. 2006;39:394–400.CrossRef
21.
go back to reference Lundy FT, Linden GJ. Neuropeptides and neurogenic mechanisms in oral and periodontal inflammation. Crit Rev Oral Biol Med. 2004;15:82–98.CrossRef Lundy FT, Linden GJ. Neuropeptides and neurogenic mechanisms in oral and periodontal inflammation. Crit Rev Oral Biol Med. 2004;15:82–98.CrossRef
22.
go back to reference Artese L, Rubini C, Ferrero G, Fioroni M, Santinelli A, Piattelli A. Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps. J Endod. 2002;28:20–3.CrossRef Artese L, Rubini C, Ferrero G, Fioroni M, Santinelli A, Piattelli A. Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps. J Endod. 2002;28:20–3.CrossRef
23.
go back to reference Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M. Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice. Am J Physiol - Hear Circ Physiol. 2011;300:H431–9.CrossRef Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M. Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice. Am J Physiol - Hear Circ Physiol. 2011;300:H431–9.CrossRef
24.
go back to reference Rechenberg DK, Galicia JC, Peters OA. Biological markers for pulpal inflammation: A systematic review. PLoS ONE. 2016;11:e0167289.CrossRef Rechenberg DK, Galicia JC, Peters OA. Biological markers for pulpal inflammation: A systematic review. PLoS ONE. 2016;11:e0167289.CrossRef
25.
go back to reference Zheng S, Li W, Xu M, Bai X, Zhou Z, Han J, Shyy JY, Wang X. Calcitonin gene-related peptide promotes angiogenesis via AMP-activated protein kinase. Am J Physiol—Cell Physiol. 2010;299:C1485–92.CrossRef Zheng S, Li W, Xu M, Bai X, Zhou Z, Han J, Shyy JY, Wang X. Calcitonin gene-related peptide promotes angiogenesis via AMP-activated protein kinase. Am J Physiol—Cell Physiol. 2010;299:C1485–92.CrossRef
26.
go back to reference Arana-Chavez VE, Massa LF. Odontoblasts: The cells forming and maintaining dentine. Int J Biochem Cell Biol. 2004;36:1367–73.CrossRef Arana-Chavez VE, Massa LF. Odontoblasts: The cells forming and maintaining dentine. Int J Biochem Cell Biol. 2004;36:1367–73.CrossRef
27.
go back to reference Sakdee JB, White RR, Pagonis TC, Hauschka PV. Hypoxia-amplified Proliferation of Human Dental Pulp Cells. J Endod. 2009;35:818–23.CrossRef Sakdee JB, White RR, Pagonis TC, Hauschka PV. Hypoxia-amplified Proliferation of Human Dental Pulp Cells. J Endod. 2009;35:818–23.CrossRef
28.
go back to reference Römer P, Wolf M, Fanghänel J, Reicheneder C, Proff P. Cellular response to orthodontically-induced short-term hypoxia in dental pulp cells. Cell Tissue Res. 2014;355:173–80.CrossRef Römer P, Wolf M, Fanghänel J, Reicheneder C, Proff P. Cellular response to orthodontically-induced short-term hypoxia in dental pulp cells. Cell Tissue Res. 2014;355:173–80.CrossRef
29.
go back to reference Olsson M, Lindqvist B. Occlusal interferences in orthodontic patients before and after treatment, and in subjects with minor orthodontic treatment need. Eur J Orthod. 2002;24:677–87.CrossRef Olsson M, Lindqvist B. Occlusal interferences in orthodontic patients before and after treatment, and in subjects with minor orthodontic treatment need. Eur J Orthod. 2002;24:677–87.CrossRef
30.
go back to reference Ren Y, Maltha JC, Kuijpers-Jagtman AM. Optimum force magnitude for orthodontic tooth movement: A systematic literature review. Angle Orthod. 2003;73:86–92.PubMed Ren Y, Maltha JC, Kuijpers-Jagtman AM. Optimum force magnitude for orthodontic tooth movement: A systematic literature review. Angle Orthod. 2003;73:86–92.PubMed
31.
go back to reference Von Böhl M, Ren Y, Fudalej PS, Kuijpers-Jagtman AM. Pulpal reactions to orthodontic force application in humans: A systematic review. J Endod. 2012;38:1463–9.CrossRef Von Böhl M, Ren Y, Fudalej PS, Kuijpers-Jagtman AM. Pulpal reactions to orthodontic force application in humans: A systematic review. J Endod. 2012;38:1463–9.CrossRef
Metadata
Title
Expression of substance P, calcitonin gene-related peptide and vascular endothelial growth factor in human dental pulp under different clinical stimuli
Authors
Javier Caviedes-Bucheli
Luis Fernando Lopez-Moncayo
Hernan Dario Muñoz-Alvear
Jose Francisco Gomez-Sosa
Luis Eduardo Diaz-Barrera
Hernando Curtidor
Hugo Roberto Munoz
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2021
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-021-01519-x

Other articles of this Issue 1/2021

BMC Oral Health 1/2021 Go to the issue